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Granulomatosis with polyangiitis (Wegener’s) (GPA) is a primary systemic vasculitis, predominantly involving microscopic blood vessels with no or scanty immune deposits. GPA is strongly associated with circulating auto-antibodies to neutrophils (ANCA) and is one of a group of conditions known as ANCAassociated vasculitis (AAV). The cause of AAV is unknown. AAV has an annual incidence of 20 per million and an approximate prevalence of 200/million. It is a multi-system autoimmune disease that causes tissue damage especially to the respiratory tract and kidneys and causes early mortality, organ failure including end-stage renal disease, and chronic morbidity. Prior to the availability of effective treatment, AAV was almost universally fatal, with a 93% mortality within 2 years due to pulmonary and renal failure. Administration of cytotoxic immunosuppression (cyclophosphamide, rituximab, methotrexate) and glucocorticoids (GC) for at least one year induces remission in approximately 80% of patients. GC are a standard of care in the treatment of AAV. High doses of GC early in disease although undeniably reduce disease activity due to their anti-inflammatory and immunosuppressive properties also increase the risk of infection particularly in the elderly and in the presence of uremia. There is a major unmet need for safer therapy that leads to sustained treatment free remission in patients with relapsing disease, which will reduce drug toxicity that results from cumulative exposure to immunosuppression and glucocorticoids.
This randomized controlled trial aims to evaluate the effects of using low-dose glucocorticoids as compared to stopping glucocorticoid treatment entirely. This study hypothesizes that participants treated with a continued low-dose of prednisone will have a clinically significant, lower relapse rate than those participants who received no GC. The specific aims include evaluating the physician decision to increase prednisone for disease relapse and evaluating the rates of flare sub-types: severe vs. non-severe, time to event (flare), health-related quality of life, safety outcomes including serious adverse events and infections, and protocol performance.
Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
- Established diagnosis of granulomatosis with polyangiitis (GPA) (verified by medical record review by the Protocol Oversight Management Team) where patients will need to meet at least 2 of the 5 for the classification of GPA, at least one of which must be criterion d or e.
The modified American College of Rheumatology (ACR) criteria are:
- Nasal or oral inflammation, defined as the development of painful or painless oral ulcers or purulent or bloody nasal discharge
- Abnormal chest radiograph, defined as the presence of nodules, fixed infiltrates, or cavities.
- Active urinary sediment, defined as microscopic hematuria (>5 red blood cells per high power field) or red blood cell casts
- Granulomatosis inflammation on biopsy, defined as histologic changes showing granulomatous inflammation within the wall of an artery or in the perivascular or extravascular area. Note: Pauci-immune glomerulonephritis seen on kidney biopsy will suffice for this criterion.
- Positive anti-neutrophil cytoplasmic antibody (ANCA) test specific for proteinase-3 measures by enzyme-linked immunoassay
Patients who are myeloperoxidase (MPO) positive or ANCA negative are still eligible for this study if they meet the criteria above and are felt to have GPA.
- Active disease within the prior 12 months (initial presentation or relapse) that at time of active disease required treatment with prednisone ≥ 20 mg/day
- Disease remission at time of enrollment
- Prednisone dose at time of enrollment of ≥ 5mg/day and ≤ 20 mg/day
- Participant age of 18 years or greater
- If the patient is taking an immunosuppressive medication agent other than prednisone (maintenance agent) then the maintenance agent must be at a stable dose for one month prior to enrollment with no plans by the treating physician to change the dose (other than for safety purposes/toxicity) for the duration of the study (through the month 6 visit or early termination). Acceptable maintenance agents include azathioprine, leflunomide, 6-mercaptopurine, methotrexate, mycophenolate mofetil, rituximab, or mycophenolate sodium. Patients may be on trimethoprim/sulfamethoxazole (TMP/SMX) for use as either a maintenance agent or for prophylaxis for infection. TMP/SMX may be used in combination with other drugs.
- 6.1 If the patient is regularly taking trimethoprim/sulfamethoxazole at any dose then the patient is eligible if there no plans by the treating physician to change the dose after enrollment (other than for dose reduction or discontinuation for safety purposes/toxicity) for the duration of the study.
- Agreement from Treating Physician that 0mg/day of prednisone or 5mg/day of prednisone is standard of care
- Participant's Treating Physician is located in the United States
- Comorbid condition that has moderate likelihood of requiring a course of prednisone within one year of enrollment (e.g. chronic obstructive pulmonary disease (COPD), asthma, adrenal insufficiency).
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
University of South Florida TAPIR Study Team, Tampa, Florida, United States, 33612